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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00750282




Registration number
NCT00750282
Ethics application status
Date submitted
9/09/2008
Date registered
10/09/2008
Date last updated
24/07/2014

Titles & IDs
Public title
Phase II Study of Florbetaben (BAY 94-9172) PET Imaging for Detection/Exclusion of Cerebral ß-amyloid in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers
Scientific title
An Open-label, Non-randomized, Multi-center Study to Optimize Image Assessment and Evaluate the Efficacy and Safety of BAY 94-9172 (ZK 6013443) Positron Emission Tomography (PET) for Detection/Exclusion of Cerebral Amyloid Beta in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers
Secondary ID [1] 0 0
2007-002256-42
Secondary ID [2] 0 0
311741
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Amyloid Beta-Protein 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Florbetaben (BAY94-9172)

Experimental: Florbetaben (BAY94-9172) -


Treatment: Drugs: Florbetaben (BAY94-9172)
Healthy volunteers and patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth - Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis.
Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used.
Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal.
Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final
Timepoint [1] 0 0
90 - 110 min after investigational medical product (IMP) injection
Primary outcome [2] 0 0
Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth. - Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity.
The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia.
Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media.
Timepoint [2] 0 0
90 - 110 min after IMP injection
Secondary outcome [1] 0 0
Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment - PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed
Timepoint [1] 0 0
45 - 60 min and 110 - 130 min after IMP injection
Secondary outcome [2] 0 0
Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score) - The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement.
Timepoint [2] 0 0
45-60 min, 90-110 min, 110-130 min
Secondary outcome [3] 0 0
Standard Uptake Value Ratios for Florbetaben Signal - The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.)
Timepoint [3] 0 0
90-110 min post injection

Eligibility
Key inclusion criteria
- Each subject / Healthy volunteer (HV) who meets the following criteria will be
eligible for enrollment into the study:

- Is a man or woman and is > 55 of age, whereby females must be without
childbearing potential (confirmed by either: age >/= 60; or history of
hysterectomy, or last spontaneous bleeding at least 2 years prior to the study
start)

- Has at least 6 years of education

- Is able to provide informed consent, understand the information provided on the
purpose and conduct of the trial and to comply with study procedures

- Possesses a general health that permits adequate compliance with all study
procedures

- The subject, or the subject and caregiver (for probable AD patients) will be
compliant and have a high probability of completing the study

- Informed consent has been signed and dated (with time) by the subject and/or the
subject's caregiver (for probable AD patients)

- Inclusion criteria for HV only:

- Has no evidence of cognitive impairment

- Has MRI brain scan that has been judged as "normal" (age- appropriate)

- Inclusion criteria for patients with AD only:

- Presents with positive assessment for dementia of Alzheimer's type

- Does not fulfill the criteria Dementia with Lewy Bodies (DLB) or Vascular
Dementia (VaD)

- MRI brain scan findings that do not reveal changes indicative of stroke and/or
generalized cerebrovascular disease

- Has a caregiver that is willing and able to attend all study visits and perform
the psychometric tests requiring the presence of a caregiver
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has any contraindication to MRI examination scan

- Is scheduled for surgery and/or another invasive procedure within the time period of
up to 24 hours following IMP application

- Is allergic to the IMP or any of its constituents and/or has a history of severe
allergic reactions to drugs or allergens (e.g. patients / volunteers with allergic
asthma)

- is critically ill and/or medically unstable and whose clinical course during the
observation period is unpredictable

- Has a history of exposure to any radiation >15 milli Sieverts (mSv)/year (e.g.
occupational or radiation therapy)

- Is receiving drug therapy or other treatment that is known to lead to greatly
fluctuating values of the hematological or chemical laboratory parameters or to severe
side effects (e.g. chemotherapy)

- Has been previously enrolled in this study or participated in a clinical study
involving an investigational pharmaceutical product within 30 days prior to screening,
and/or any radiopharmaceutical

- Has a brain tumor or other intracranial lesion, a disturbance of cerebro-spinal fluid
(CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of head
trauma or brain surgery

- Has an inflammatory or infectious central nervous system (CNS) disease, e.g. multiple
sclerosis, HIV, syphilis, or Creutzfeldt-Jacob disease

- Has a history, physical, laboratory or imaging findings indicative of a neurological
or psychiatric illness

- Has another disease that can cause disturbance of brain function (e.g. vitamin B12 or
folic acid deficiency, disturbed thyroid function)

- Has a history of alcohol or drug abuse

- Has history of severe persistent depression

Study design
Purpose of the study
Diagnosis
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Adelaide
Recruitment hospital [3] 0 0
- Heidelberg
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Rhode Island
Country [6] 0 0
Germany
State/province [6] 0 0
Bayern
Country [7] 0 0
Germany
State/province [7] 0 0
Nordrhein-Westfalen
Country [8] 0 0
Germany
State/province [8] 0 0
Sachsen
Country [9] 0 0
Germany
State/province [9] 0 0
Berlin
Country [10] 0 0
Japan
State/province [10] 0 0
Hyogo
Country [11] 0 0
Japan
State/province [11] 0 0
Tokyo
Country [12] 0 0
Switzerland
State/province [12] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Life Molecular Imaging SA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK
6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque
(amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein
accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is
therefore a potential tracer to be used for detecting amyloid plaques. For each subject it is
required to visit the study centre during the screening phase, on the PET imaging day and for
1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7
days after IMP administration. During the screening phase the subject's medical, neurological
and surgical history, specific laboratory tests related to AD, MRI of the brain and certain
neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations,
vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET
imaging day before IMP injection and monitored during and after two PET imaging sessions.
Clinical safety measures will be performed again on the follow-up visit next day. The results
of PET imaging with IMP will be compared between probable AD patients and healthy volunteers
(HV). The clinical diagnosis is based on international validated and accepted criteria and
established after comprehensive clinical and neuro-psychiatric examinations
Trial website
https://clinicaltrials.gov/show/NCT00750282
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications